The Investigator has previously established that a hairpin ribozyme designed to cleave the 5' leader sequence of HIV-1 RNA can confer resistance against virus challenge to human T-cell lines, primary T-lymphocytes, and to macrophage lineage cells derived from transduced CD34+ precursors in vitro. These studies formed the basis for the parent grant to this application, which focused on studies of transduction and expression of the hairpin ribozyme in hematopoietic progenitor cells in vitro. The Principal Investigator has initiated a collaboration with Dr. Ahrlund- Richter at the Karolinska Institute in Sweden, who has developed a transgenic mouse model which expresses an active hammerhead ribozyme designed to target cellular beta 2 microglobulin RNA. The current application centers around developing a transgenic mouse model to determine the toxicity, relative levels of expression, persistence of expression and efficacy against the target HIV-1 RNA sequences of certain hairpin ribozymes in vivo. Additional studies will determine the relative efficacy of specific ribozymes of the hairpin versus hammerhead type, to cleave the identical HIV 1 RNA target sequence in vitro and in vivo. An additional goal of this application is to develop an RNA based anti HIV 1 vector for use in clinical trials based at the Karolinska Institute.